Table 1.

Vertebrate PCP components and modulators, their role in PCP signaling, and their involvement in cancer

GeneStructureFunction in PCPInvolvement in cancer
Upstream PCP components
    Wnt 5a,11Secreted glycoproteinInitiate PCP signalingPromote or inhibit cancer (context dependent)
    FatProtocadherinCell adhesion and signalingDeletion or silencing in oral squamous carcinoma
    DachsousProtocadherinCell adhesion and signalingTumor suppressor gene
    Four-jointedGolgi kinasePhosphorylate cadherin domains of Fat and DachsousUnknown
    AtrophinTranscriptional corepressorBind cytoplasmic tail of FatAltered expression in neuroblastoma
Core PCP components
    Frizzled7-Transmembrane receptorRecruit Dvl to membrane upon binding WntUpregulated in cancer
    DishevelledCytoplasmic proteinRecruited to membrane by FzdUpregulated in cancer
    Vangl4 -Transmembrane proteinBind Dvl and PKCδHigh expression in metastatic tissue
    Celsr7-Transmembrane protocadherinRegulate asymmetrical localization of FzdUnknown
    PrickleCytoplasmic proteinAntagonize Dvl recruitment by FzdDownregulated in hepatocellular carcinoma
Downstream PCP effectors
    Daam1ForminBridge Dvl and RhoAUnknown
    RhoASmall GTPaseRegulate cytoskeleton downstream of Daam1Upregulated in cancer
    RacSmall GTPaseRegulate cytoskeleton downstream of DvlUpregulated in cancer
    JNKS/T protein kinaseRegulate cytoskeleton downstream of RacUpregulated in cancer
    RockRho kinaseRegulate cytoskeleton downstream of RhoUpregulated in cancer
    ProfilinG-actin-binding proteinBind DAAM1Low expression in breast, pancreatic, and hepatic cancer
PCP Modulators
    Paraxial protocadherinProtocadherinPromote Dvl recruitment to membraneDownregulated in breast cancer
    EphrinB1Transmembrane ligand for EphBind Dvl and activate RhoPromote cancer cell invasion
    PKCδPKC kinaseBind and activate Dvl for membrane recruitmentBreast cancer progression
    Sprouty1Cytoplasmic proteinInhibit Dvl recruitment to membraneTumor suppressor gene
    Cthrc1Secreted glycoproteinForm Cthrc1-Wnt-Fzd complex to promote PCPUpregulated in invasive cancer
    Ptk7Transmembrane protein tyrosine pseudokinaseCooperate with Fzd to localize DvlExpressed in cancer